{"doi":"10.1126/sciimmunol.abq7486","title":"Transcriptional programming of CD4 <sup>+</sup> T <sub>RM</sub> differentiation in viral infection balances effector- and memory-associated gene expression","abstract":"After resolution of infection, T cells differentiate into long-lived memory cells that recirculate through secondary lymphoid organs or establish residence in tissues. In contrast to CD8 + tissue-resident memory T cells (T RM ), the developmental origins and transcriptional regulation of CD4 + T RM remain largely undefined. Here, we investigated the phenotypic, functional, and transcriptional profiles of CD4 + T RM in the small intestine (SI) responding to acute viral infection, revealing a shared gene expression program and chromatin accessibility profile with circulating T H 1 and the progressive acquisition of a mature T RM program. Single-cell RNA sequencing identified heterogeneity among established CD4 + T RM , which were predominantly located in the lamina propria, and revealed a population of cells that coexpressed both effector- and memory-associated genes, including the transcriptional regulators Blimp1, Id2, and Bcl6. T H 1-associated Blimp1 and Id2 and T FH -associated Bcl6 were required for early T RM formation and development of a mature T RM population in the SI. These results demonstrate a developmental relationship between T H 1 effector cells and the establishment of early T RM , as well as highlighted differences in CD4 + versus CD8 + T RM populations, providing insights into the mechanisms underlying the origins, differentiation, and persistence of CD4 + T RM in response to viral infection.","journal":"Science Immunology","year":2023,"id":328910,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9521,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":108902,"name":"Kennidy K. Takehara","orcid":"0000-0002-1990-155X","position":1,"is_corresponding":false},{"id":297335,"name":"Tianda Deng","orcid":"0000-0002-7795-350X","position":2,"is_corresponding":false},{"id":1051450,"name":"Shannon O’Shea","orcid":null,"position":3,"is_corresponding":false},{"id":841747,"name":"Maximilian Heeg","orcid":"0000-0002-9594-1377","position":4,"is_corresponding":false},{"id":236067,"name":"Kyla Omilusik","orcid":"0000-0003-3675-048X","position":5,"is_corresponding":false},{"id":84671,"name":"J. Justin Milner","orcid":"0000-0002-0752-2130","position":6,"is_corresponding":false},{"id":618277,"name":"Sara Quon","orcid":"0000-0003-3860-3491","position":7,"is_corresponding":false},{"id":259945,"name":"Matthew E. Pipkin","orcid":"0000-0002-9688-0190","position":8,"is_corresponding":false},{"id":104940,"name":"Jinyong Choi","orcid":"0000-0003-2474-2837","position":9,"is_corresponding":false},{"id":103780,"name":"Shane Crotty","orcid":"0000-0002-6484-6262","position":10,"is_corresponding":false},{"id":61594,"name":"Ananda W. Goldrath","orcid":"0000-0002-5900-508X","position":11,"is_corresponding":false},{"id":569834,"name":"Quynh Nguyen","orcid":"0000-0002-5975-3600","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-19T01:08:56.940647Z","pmid":"37172104","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}